Risk of opioid overdose during buprenorphine treatment for opioid use disorder in the fentanyl era

For patients who use fentanyl, higher than currently recommended maintenance doses of buprenorphine treatment for opioid use disorder (OUD) may be needed to prevent cravings and withdrawal, but some clinicians and regulators are concerned that higher doses may increase overdose risk. We evaluated buprenorphine effectiveness for overdose prevention in the fentanyl era.

We conducted a retrospective cohort study of Rhode Island residents initiating buprenorphine for OUD (October 2016‒September 2022) using statewide administrative data. On each of 365 follow-up days, patients were classified as having an active buprenorphine prescription (yes/no) and a non-fatal or fatal opioid overdose (yes/no). Follow-up was discontinued if patients died or initiated methadone or naltrexone. Generalized estimating equations compared opioid overdose risk for days with versus without an active buprenorphine prescription, controlling for potential confounders and clustering by patient.

Among 8,676 patients initiating buprenorphine, most were aged 25-44 years (56.0 %) and male (61.3 %). In the 365 days following initiation, 52.6 % of person-days were covered by an active buprenorphine prescription, 1,069 patients (12.3 %) had follow-up discontinued due to methadone initiation, and 411 patients (4.7 %) experienced 545 opioid overdoses. Opioid overdose risk was 61 % lower for days with versus without an active buprenorphine prescription (adjusted risk ratio = 0.39, 95 % confidence interval = 0.31-0.49). Daily doses prescribed on days with and without an opioid overdose event were similar (P = 0.261).

Buprenorphine remains effective for overdose prevention in the fentanyl era among patients who remain in treatment. There was no evidence that higher doses were associated with greater overdose risk.